Details

Autor(en) / Beteiligte

• Nguyen, Linh
• McCord, Kelli A
• Bui, Duong T
• Bouwman, Kim M
• Kitova, Elena N
• Elaish, Mohamed
• Kumawat, Dhanraj
• Daskhan, Gour C
• Tomris, Ilhan
• Han, Ling
• Chopra, Pradeep
• Yang, Tzu-Jing
• Willows, Steven D
• Mason, Andrew L
• Mahal, Lara K
• Lowary, Todd L
• West, Lori J
• Hsu, Shang-Te Danny
• Hobman, Tom
• Tompkins, Stephen M
• Boons, Geert-Jan
• de Vries, Robert P
• Macauley, Matthew S
• Klassen, John S

Titel

Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2

Ist Teil von

• Nature chemical biology, 2022-01, Vol.18 (1), p.81-90

Ort / Verlag

United States

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Emerging evidence suggests that host glycans influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we reveal that the receptor-binding domain (RBD) of the spike (S) protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (Sia), with preference for monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind to the RBD. The monomeric affinities (K  = 100-200 μM) of gangliosides for the RBD are similar to another negatively charged glycan ligand of the RBD proposed as a viral co-receptor, heparan sulfate (HS) dp2-dp6 oligosaccharides. RBD binding and infection of SARS-CoV-2 pseudotyped lentivirus to angiotensin-converting enzyme 2 (ACE2)-expressing cells is decreased following depletion of cell surface Sia levels using three approaches: sialyltransferase (ST) inhibition, genetic knockout of Sia biosynthesis, or neuraminidase treatment. These effects on RBD binding and both pseudotyped and authentic SARS-CoV-2 viral entry are recapitulated with pharmacological or genetic disruption of glycolipid biosynthesis. Together, these results suggest that sialylated glycans, specifically glycolipids, facilitate viral entry of SARS-CoV-2.